Tendon injuries such as those of repetitive overuse and cumulative trauma (e.g., carpal tunnel syndrome) are a major source of pain and disability, yet the mechanism of low-level injury and progression of tendon pathology is unknown. Animal models of tendon healing, while important, do not provide insight into the response of tendons to cumulative wear and tear. A comprehensive series of experiments is proposed herein to systematically characterize damage initiation and progression resulting from controlled levels of imposed mechanical fatigue. A novel mechanical testing protocol will be developed and implemented to reproducibly induce increasing levels of tendon damage which will be quantified using engineering damage parameters. Additional indices of tendon viscoelastic behavior will be obtained from mathematical modeling of the experimental data. Microstructural studies on fatigue-loaded tendons will be used to define the physical manifestation of fatigue damage and to correlate the structural changes with mechanical measures of degradation. Successful completion of these proposed studies will establish the necessary damage-degradation relationships needed to assess in vivo cellular responses following tendon injury.